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We conducted a two-sample Mendelian randomization analysis to determine whether those associations are causal. Independent genetic variants associated with body mass index (BMI), waist circumference (with and without adjustment for BMI), type 2 diabetes, smoking, and alcohol, coffee and caffeine consumption at the genome-wide significance level were selected as instrumental variables. Summary-level data for GERD were available from a genome-wide association meta-analysis of 71,522 GERD cases and 261,079 controls of European descent from the UK Biobank and QSkin Sun and Health studies. The odds ratio (OR) of GERD was 1.49 (95% confidence interval (CI), 1.40\u20131.60) for one standard deviation (SD) increase in BMI, 1.07 (95% CI, 1.04\u20131.10) for one-unit increase in log-transformed OR of type 2 diabetes, and 1.41 (95% CI, 1.31\u20131.52) for one SD increase in prevalence of smoking initiation. There were suggestive associations with GERD for higher genetically predicted waist circumference (OR per one SD increase, 1.14, 95% CI, 1.02\u20131.26) and caffeine consumption (OR per 80\u00a0mg increase, 1.08, 95% CI, 1.02\u20131.15). Genetically predicted waist circumference adjusted for BMI, alcohol or coffee consumption was not associated GERD. This study suggests causal roles of adiposity, diabetes, and smoking, and a possible role of high caffeine consumption in the development of GERD.<\/jats:p>","DOI":"10.1007\/s10654-022-00842-z","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T16:59:40Z","timestamp":1643993980000},"page":"747-754","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Adiposity, diabetes, lifestyle factors and risk of gastroesophageal reflux disease: a Mendelian randomization study"],"prefix":"10.1007","volume":"37","author":[{"given":"Shuai","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-0341","authenticated-orcid":false,"given":"Susanna C.","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"issue":"2","key":"842_CR1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1053\/j.gastro.2017.07.045","volume":"154","author":"JE Richter","year":"2018","unstructured":"Richter JE, Rubenstein JH. 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